Organization and reorganization of neuromuscular junctions in mice lacking neural cell adhesion molecule, tenascin-C, or fibroblast growth factor-5.
Many proteins have been hypothesized to mediate intercellular interactions that regulate the formation, maturation, and maintenance of the skeletal neuromuscular junction. Three of the best characterized of these are a membrane-associated adhesion molecule, neural cell adhesion molecule (N-CAM), an extracellular matrix component, tenascin-C, and a soluble growth factor, fibroblast growth factor-5 (FGF-5). To assess the roles of these molecules in synaptogenesis in vivo, we examined neuromuscular junctions in homozygous mutant mice lacking N-CAM, tenascin-C, FGF-5, or both N-CAM and tenascin-C. End plates were 14% smaller in N-CAM-deficient mice than in controls, and formation of junctional folds was delayed in this mutant. In all other respects tested, however, the structure and molecular architecture of neuromuscular junctions were normal in all three single mutants and in the double mutant. We also tested the abilities of damaged motor axons to reinnervate mutant muscle after axotomy and of intact motor axons to sprout after partial denervation. Again, no significant differences among genotypes were observed. Together, these results demonstrate that N-CAM, tenascin-C, and FGF-5 are dispensable for major aspects of synaptic development and regeneration.
Moscoso
L M
LM
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cremer
H
H
Sanes
J R
JR
D000818:Animals; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009154:Mutation / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D019063:Tenascin / Q000172:deficiency*
C496450:Fgf5 protein, mouse; D019006:Neural Cell Adhesion Molecules; D019063:Tenascin; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors